Gene therapy is an active area of research, and expectation for successful therapy is extremely high. In gene therapy approaches in which the gene per se is the medicine, the therapy for disease is conducted by transferring a gene of a designated enzyme, cytokine, and the like into cells of a patient. The introduced gene then produces the designated substance in the patient's body. This gene therapy can be divided to two types. The purpose of the first type is semipermanent expression of designated gene by integrating the gene into genome of a patient. The purpose of another type is transient expression of a gene without expectation of its integration into genome. In the latter type of gene therapy, a method using adenovirus and the like is often adopted as a method for transferring into the patient a gene encoding, for example, a cytokine which increases immuno-potency against cancer cells (Cardiovascular Research, 28, 445 (1994); Science, 256, 808 (1992); Gastroenterology, 106, 1076 (1994); TIBTECH, 11, 182 (1993); J. Biol. Chem., 266, 3361 (1991); Nature Medicine, 1, 583, (1995); and references cited therein).
In the case of using a virus vector, though the efficiency of gene transfer is generally high, repeated administrations are difficult due to immune responses (J. Biol. Chem., 269, 13695 (1994), Am. J. Respir. Cell Mol., 10, 369 (1994)).
A preparation using collagen for gradually releasing medicines containing organic compounds or a protein preparation is disclosed in J. Controlled Release 33, 307–315 (1995), etc. However, the disclosed and usual medicine (for example, protein drug, medicine chemically synthesized, etc.) is dissolved in approximately 1–2 days when retained in, for example, collagen gel.
In a method which is presently used in gene therapy and comprises administering a gene vector (a gene-inserted vector) or a gene directly, the gene vector or the gene contacts cells immediately after administration, and immediately after that gene transfer starts and is completed at once. Furthermore, the gene transduced into cells is diluted (that is, its copy number decreases) with cell division or is reduced by degradation in cells. Therefore, expression of the transferred gene can be maintained only for several weeks which is too short to practice sufficient treatment and this is a deficiency in the method. Accordingly, repeated administrations of a gene vector or a gene are necessary. Therefore, an object of the present invention is to overcome these defects and provide a preparation, which can release a gene vector or a gene gradually and can maintain the therapeutic effect for a long time.
Furthermore, a method enabling repeated administrations is expected, because those are difficult in gene therapy using a virus vector and the like. Accordingly, a second object of the present invention is to provide a gene preparation enabling repeated administrations in gene therapy using a virus vector and the like.
Furthermore, it is desirable that gene expression in the body can be stopped any time to ensure safety, because a gene is expressed for several weeks, which is longer than the term for a protein preparation. Accordingly, a third object of the present invention is to provide a gene preparation which can make it possible to quickly stop the gene transfer when termination of treatment is intended.